The relationship between visual hallucinations, functioning, and suicidality over the course of illness: a 10-year follow-up study in first-episode psychosis

Visual hallucinations in psychosis are under-researched despite associations with increased illness severity, functional impairments, and suicidality in the few existing studies. Further, there are no long-term longitudinal studies, making it impossible to conclude if these associations are state or trait phenomena. In the current prospective longitudinal study, 184 individuals with first-episode psychosis were assessed with semi-structured clinical interviews and self-report questionnaires at baseline and 10-year follow-up. Participants were grouped based on lifetime experience of visual hallucinations: before or at baseline (VH+/+), first during follow-up (VH−/+), or never (VH−/−). Associations with functioning, suicide attempts, childhood trauma and other markers of illness severity were tested using multinomial logistic regression analysis. At baseline, the VH+/+ group (37.5%), but not VH−/+ (12.5%), had poorer functioning, higher symptom severity, a lower age at onset, and included more individuals with a history of multiple suicide attempts than the VH−/− group (50%). At follow-up, the VH−/+ group, but not VH+/+, had poorer functioning and higher symptom severity than the VH−/− group. However, the number of participants who committed multiple suicide attempts during the follow-up period was again significantly higher in the VH+/+ group. There was no association with childhood trauma. Hence, visual hallucinations are associated with impaired functioning and higher symptom severity, but only in the short-term. However, visual hallucinations that arise early in the course of illness are a risk indicator for repeated suicide attempts throughout the illness course. These findings highlight the relevance of assessing visual hallucinations and monitoring their development over time.


Comparison of study participants with those lost to follow-up
Of all participants who were deemed eligible for study participation at baseline and for whom SCID-I based ratings of lifetime experience of visual hallucinations were available (N = 454), 57% (n = 261) were lost to follow-up.Of these, 150 had withdrawn from participation, 69 could not be located, 23 had moved abroad, and 19 had died.For nine out of the remaining 193 followed-up participants, SCID-I information assessed at follow-up was incomplete, and they were therefore excluded from the current study.
To evaluate the representativeness of the final sample included in this study (n = 184), comparisons with those lost to follow-up were conducted.Groups were compared on a range of baseline variables central to the current study.In addition, national health registry data was accessed to compare the amount of time spent in specialized health services during what would constitute a participant's 10-year follow-up period.Dates of contacts with specialized health services were counted as full days and summarized both across different levels of care, and per level of care, with level of care corresponding to either inpatient care, outpatient contacts, or day treatment.Only contacts where the primary reason was due to schizophrenia spectrum diagnoses (ICD-10 codes F20-F29), bipolar disorder (F31) or depressive episodes (F32) were included in this summary.Since the time period covered by the available registry data only ranged from 01.01.2008 to 31.12.2020,information was incomplete for follow-up years falling outside of this time range.Therefore, the average number of days spent in specialized health care per year was calculated based on all follow-up years for which information was complete.
Descriptive and test statistics of baseline variables are presented in Table S1.

Table S1
Descriptive and test statistics of baseline variables by follow-up status The participant group lost to follow-up included significantly more male participants (61.7%) than the final group of study participants (51.1%;Table S1).Rates of bipolar disorder were lower in the group lost to follow-up (17.2%) than in the final study sample (29.3%), and rates of other psychosis slightly higher (32.2%;Table S1).While there were no differences in lifetime experience of visual hallucinations (Table S1), the percentage of participants with a history of multiple suicide attempts was significantly larger in the final study sample (16.8%) than in the group that was lost to follow-up (6.9%;Table S1).
To assess whether this difference in past suicide attempts could be explained by the differences in gender and bipolar disorder rates, a logistic regression was fitted to predict follow-up status (included in study vs. lost to follow-up) by gender (reference: male), diagnosis This indicates that participants with bipolar disorder and participants with a history of multiple suicide attempts are overrepresented in the final study sample, and that this cannot be explained by higher rates of female participants in this group.Given the absence of group differences in rates of visual hallucinations, this bias does not affect the main analyses of this study, namely the investigation of the association between visual hallucinations, suicidality, and functioning.However, it does mean that the presented rates of multiple suicide attempts may not be representative of the general FEP population.
There were no significant differences in average number of days spent in specialized health care per year within the follow-up period.This was true across levels of care (U =

Psychiatric comorbidities at baseline
Total number of psychiatric comorbidities were similar for all VH groups (see Table 1, main article).An overview of all comorbidities per group is presented in Table S2.

Multivariable analyses
To test if other markers of illness severity influenced the associations between VHgroup status, functioning, and suicidality, multivariable models were constructed for both baseline (Table S3) and follow-up analyses (Table S4), including all variables with a statistically significant association with VH-group in bivariate analyses.

Table S3
Multivariable multinomial logistic regression including baseline variables

PANSS analyses excluding item p3 ('hallucinatory behavior')
The PANSS total score includes ratings of hallucinatory behavior (item p3) without specification by modality.Therefore, and because the PANSS assesses current symptom severity whereas visual hallucinations were assessed in a dichotomized manner and according to lifetime experience, item p3 remained included in the PANSS total score for all main analyses.Nevertheless, here we provide supplementary analyses using a reduced PANSS total score calculated after exclusion of item p3.Results of bivariate and multivariable analyses are presented.
Similarly, there was no change in multivariable analysis results, with direction, size, and significance of effects similar to the model including the PANSS total score (Table S6).

Table S6
Multivariable multinomial logistic regression including follow-up variables

Figure S1 PANSS
Figure S1PANSS sum scores at baseline and follow-up, with and without hallucinatory behavior Alcohol and Substance add./abu.= presence of an alcohol or substance addiction or abuse disorder, Bipolar NOS = bipolar not otherwise specified, OCD = Obsessive-compulsive disorder, PTSD = Post-traumatic stress disorder.Single individuals may be represented in multiple diagnosis categories.
a Personality disorders were not assessed systematically but only when necessary for differential diagnoses.

Table S5
Multivariable multinomial logistic regression including baseline variables